mpt53 Resolved · high auto-curated

H37Rv Rv2878c · MTBC0 mtbc0_003061 · 173 aa · 3209542–3210063 (-) · RefSeq NP_217394.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)soluble secreted antigen Mpt53
MTBC0 PGAP re-annotationprotein disulfide oxidoreductase
Revised (this work)Protein disulfide oxidoreductase. Pfam: AhpC-TSA (PF00578.28), Redoxin (PF08534.17), Thioredoxin_2 (PF13098.14).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WG65 SwissProt · reviewed · Evidence at protein level
UniProt nameSoluble secreted antigen MPT53
Curated functionDisulfide oxidoreductase that catalyzes the oxidation of reduced, unfolded secreted proteins to form disulfide bonds. Despite a weak homology to thioredoxin this cannot serve as a substrate for thioredoxin reductase.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
O Post-translational modification, protein turnover, chaperones
Preferred namempt53
eggNOG descriptionSoluble secreted antigen Mpt53
Orthologous groupCOG0526
Gene Ontology (16) GO:0003674, GO:0003824, GO:0005575, GO:0005576, GO:0008150, GO:0008152, GO:0009987, GO:0016491, GO:0019725, GO:0042592, GO:0045454, GO:0050789 +4 more

Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.

Conservation & selection (intra-MTBC, 145 209 strains)

pN/pS 1.664 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 5 missense, 0 nonsense, 0 frameshift

pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.

Domains (Pfam, hmmscan --cut_ga)

PfamAccessioni-EvalueResiduesDescription
AhpC-TSAPF00578.28 9.1e-1543–144 AhpC/TSA family
RedoxinPF08534.17 2.7e-1144–137 Redoxin
Thioredoxin_2PF13098.14 2.1e-0657–151 Thioredoxin-like domain

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: Rv2877c (integral membrane protein), high confidence from genomic context alone (score 976 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2877c integral membrane protein 995 976 ctx neighborhood:798 cooccurence:719 coexpression:619 textmining:813
Rv2428 ahpC alkyl hydroperoxide reductase subunit AhpC 843 830 experimental:468 database:611
Rv0137c msrA peptide methionine sulfoxide reductase MsrA 832 822 experimental:562 database:596
Rv0462 lpdC dihydrolipoamide dehydrogenase 754 743 experimental:410 database:550
Rv0794c oxidoreductase 754 743 experimental:410 database:550
Rv2713 sthA pyridine nucleotide transhydrogenase 754 743 experimental:410 database:550
Rv2855 mtr mycothione reductase 752 741 experimental:410 database:550
Rv3303c lpdA NAD(P)H quinone reductase LpdA 752 741 experimental:410 database:550
Rv3672c hyp hypothetical protein 733 724 coexpression:648
Rv3051c nrdE ribonucleoside-diphosphate reductase subunit alpha 715 702 database:578
Rv0570 nrdZ vitamin B12-dependent ribonucleoside-diphosphate reductase 713 699 database:578
Rv0432 sodC superoxide dismutase 674 654 database:595
Rv2674 msrB peptide methionine sulfoxide reductase MsrB 674 654 database:594
Rv0038 hyp hypothetical protein 637 624 database:602
Rv1937 oxygenase 666 616 database:506

STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.

Evidence

  • Legacy H37Rv annotation: soluble secreted antigen Mpt53
  • MTBC0 PGAP product: protein disulfide oxidoreductase
  • Pfam (hmmscan --cut_ga): AhpC-TSA PF00578.28 (E=9e-15), Redoxin PF08534.17 (E=3e-11), Thioredoxin_2 PF13098.14 (E=2e-06)
  • (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)

Sources

  • Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
  • Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_217394.1)
  • Domains: Pfam-A via hmmscan --cut_ga — AhpC-TSA (PF00578.28), Redoxin (PF08534.17), Thioredoxin_2 (PF13098.14)
  • Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
  • Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021, doi:10.1093/molbev/msab293), eggNOG 5.0 DB (Huerta-Cepas et al. 2019) — OG COG0526
  • Curated reference: UniProt P9WG65 (SwissProt, reviewed; Evidence at protein level)
  • Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 107 functional partner(s); context anchor Rv2877c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003061|Rv2878c|mpt53
MSLRLVSPIKAFADGIVAVAIAVVLMFGLANTPRAVAADERLQFTATTLSGAPFDGASLQGKPAVLWFWTPWCPFCNAEAPSLSQVAAANPAVTFVGIATRADVGAMQSFVSKYNLNFTNLNDADGVIWARYNVPWQPAFVFYRADGTSTFVNNPTAAMSQDELSGRVAALTS